Poly(adenosine diphosphate-ribose) polymerase as therapeutic target: lessons learned from its inhibitors

// Anna Maria Cseh 1, 2 , Zsolt Fabian 3 , Balazs Sumegi 1 and Luca Scorrano 2 1 Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, Pecs, Hungary 2 Department of Biology, University of Padova, Padova, Italy 3 Conway Institute, University College Dublin, Belfield, Dublin, Ireland Correspondence to: Anna Maria Cseh, email: anna.cseh@aok.pte.hu Keywords: PARP, mitochondria, cancer, signaling, targeted therapy Received: February 10, 2017      Accepted: March 28, 2017      Published: April 05, 2017 ABSTRACT Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide to a variety of target proteins. Although they have been considered as resident nuclear elements of the DNA repair machinery, recent works revealed a more intricate physiologic role of poly(ADP-ribose) polymerases with numerous extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in fundamental cellular processes like chromatin remodelling, transcription or regulation of the cell-cycle. These new insight into the physiologic roles of poly(ADP-ribose) polymerases widens the range of human pathologies in which pharmacologic inhibition of these enzymes might have a therapeutic potential. Here, we overview our current knowledge on extranuclear functions of poly(ADP-ribose) polymerases with a particular focus on the mitochondrial ones and discuss potential fields of future clinical applications.